Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort
Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort
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中国黑色素瘤患者中 BRAF V600E 突变的患病率：432 例队列中 BRAF 和 NRAS 突变的大规模分析
DOI：
10.1016/j.ejca.2011.06.056
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发表时间：
2012-01-01
影响因子：
8.4
通讯作者：
Guo, Jun
中科院分区：
文献类型：
--
作者：
Si, Lu;Kong, Yan;Guo, Jun
背景：NRAS和BRAF突变在高加索人黑色素瘤中有报道。然而，BRAF和NRAS突变在亚洲人群的地位和临床意义还没有被调查在一个大的scale.Methods：黑色素瘤样本（n = 432）进行了分析突变的BRAF基因的外显子11和15，和外显子1和2的NRAS基因的基因组DNA聚合酶链反应（PCR）扩增和桑格测序。结果：BRAF和NRAS基因体细胞突变的发生率分别为25.5%（110/432）和7.2%（31/432）。在110例BRAF突变患者中，98例患者（89.1%）存在V600 E突变。无慢性日光损伤的黑色素瘤（非CSD）更可能（P < 0.01）显示BRAF突变，而NRAS突变频率在黑色素瘤亚型之间无偏倚。BRAF（P < 0.01）或NRAS（P = 0.04）基因突变的患者分别比无BRAF或NRAS突变的患者更容易发生溃疡。BRAF（P = 0.003）和NRAS基因突变（P = 0.031）均与总生存期呈负相关。最常见的BRAF突变类型是V600 E。BRAF或NRAS基因突变的患者常出现溃疡，BRAF或NRAS基因突变是预后不良的指标。我们的研究可能需要在中国和亚洲黑色素瘤患者中进行靶向BRAF V600 E的激酶抑制剂的临床试验。皇冠版权所有（C）2011由爱思唯尔有限公司出版。保留所有权利。
Background: Mutations of NRAS and BRAF have been described in Caucasian melanomas. However, the status and the clinical significance of BRAF and NRAS mutations in the Asian population have not been investigated on a large scale.Methods: Melanoma samples (n = 432) were analysed for mutations in exons 11 and 15 of the BRAF gene, and exons 1 and 2 of the NRAS gene in genomic DNA by polymerase chain reaction (PCR) amplification and Sanger sequencing. Mutations of BRAF and NRAS genes were correlated to clinicopathologic features and prognosis of the patients.Results: The incidence of somatic mutations within the BRAF and NRAS genes was 25.5% (110/432) and 7.2% (31/432), respectively. Among the 110 patients with BRAF mutations, 98 patients (89.1%) had V600E mutations. Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P < 0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes. Patients with genetic mutations in BRAF (P < 0.01) or NRAS (P = 0.04) gene are more likely to have ulceration as compared to patients without BRAF or NRAS mutations, respectively. Both BRAF (P = 0.003) and NRAS mutations (P = 0.031) are inversely correlated to overall survival.Conclusions: BRAF mutation is frequent while mutations in NRAS gene are rare. The most prevalent BRAF mutation type is V600E. Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis. Our study may warrant a clinical trial of kinase inhibitors targeting BRAF V600E in Chinese and Asian melanoma patients. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.